REDWOOD CITY,
Calif.—Sickle cell disease (SCD) is recognized as an important global public health problem with more than 300,000 annual births affected by it, the
vast majority of which take place in Sub-Saharan Africa and India. In Africa, 4 percent of mortality in children younger than 5 is attributed to SCD, but
this figure approaches 16 percent of all live births in high-prevalence countries in Western Africa. In these countries, 50 to 90 percent of babies born with
SCD do not survive to adulthood. While universal newborn SCD screening is the norm in the United States, it is too expensive and impractical in places like
Africa and India.

Capnia Inc., which develops products based on its
proprietary technologies for precision metering of gas flow, has been awarded a Small Business Innovation Research (SBIR) Phase I grant to help fund the
development of a modified CoSense device that is suitable for field use in developing countries with high prevalence of SCD, also known as sickle cell anemia
(SCA). This six-month grant from the National Heart, Lung and Blood Institute (NHLBI), a division
of the National Institutes of Health (NIH), totals approximately $220,000.

According to Dr. Anish Bhatnagar, CEO of Capnia, “Studies have shown that when SCD is diagnosed in the newborn period,
early mortality is preventable through prophylactic antibiotics, vaccinations and health education. While CoSense can be used in healthcare-related
environments in developing countries, it would be desirable to extend its ability to be used in more remote settings. We are pleased that the NHLBI has
recognized the potential of our technology and will be supporting the effort with this grant.”

Based on the
Sensalyze technology platform, CoSense is a portable, non-invasive device that rapidly and accurately measures carbon monoxide (CO) in exhaled breath.
CoSense, which has 510(k) clearance for sale in the United States and has received CE Mark certification for sale in the European Union, monitors CO from
internal sources (such as hemolysis, a dangerous condition in which red blood cells degrade rapidly) and external sources (such as CO poisoning and smoke
inhalation). The initial target market is newborns with jaundice that are at risk for hemolysis, comprising approximately three million births in the United
States and European Union. Capnia’s proprietary therapeutic technology uses nasal, non-inhaled CO2 and is being evaluated to treat the
symptoms of allergies, as well as the trigeminally mediated pain conditions such as cluster headache, trigeminal neuralgia and migraine.

This grant is supported by a recently published, peer-reviewed study titled “Point-of-Care End-Tidal Carbon Monoxide
Reflects Severity of Hemolysis in Sickle Cell Anemia,” in which CoSense accurately distinguished children with SCA from age-matched healthy controls by
measuring end-tidal carbon monoxide (ETCO) with a simple, rapid, non-invasive breath test. ETCO may be a valuable tool for ongoing non-invasive monitoring of
the severity of hemolysis in SCA and ETCO has potential for use as a point-of-care screening test for SCA. This SBIR-funded project seeks to initiate
development of a point-of-care CoSense device that accurately and consistently measures ETCO under the more extreme temperature conditions encountered in
developing countries. Research and development work supported by this NHLBI grant will be conducted in collaboration with the UCSF Benioff Children’s Hospital Oakland of the University of California, San Francisco (UCSF). Dr. Ashutosh Lal, director of the thalassemia program and the
principal investigator for the published SCA study, will collaborate with Capnia for this grant.

When heme (the
red pigment) in red blood cells is broken down, CO is produced in parts-per-million quantities. This is ultimately exhaled through the breath and, if
measured precisely, is the gold standard for the detection of hemolysis. CoSense works by measuring very small amounts of carbon monoxide in the innermost
part of the lungs. Virtually all breath diagnostic devices available today need some kind of effort or maneuver from the patients. Because these devices are
targeted to the low breath rates and large tidal volumes of adults, they cannot accurately work in babies or young children. CoSense measures CO in these
populations in a non-invasive manner in a few seconds. It is done at the bedside and often with the baby in the mother’s arms.

The commercial potential of CoSense is substantial, according to Capnia. Of the 9.2 million babies born annually in the
United States and European Union, more than 60 percent will present with jaundice at some point in the first five days of life. It is estimated that about 30
percent of these are at risk for hemolysis and comprise the primary target market for CoSense. Since 2004, the American Academy of Pediatrics (AAP) has
recommended the measurement of ETCO in newborns, but CoSense is reportedly the first commercially available device that enables physicians to follow these
AAP guidelines.